1. Field of the Invention.
This invention relates to the use of certain chemicals of the benzanilide family in the therapy of immune diseases.
2. Description of the Prior Art.
Several attempts have been made in the prior art to find immunosuppressive agents with a specific chemotherapeutic application. Antimetabolic or antiproliferative agents that have been recognized largely from cancer screening, such as 6-mercaptopurine or cyclophosphamide, are effective in the therapy of autoimmune diseases, some infection allergies and dermatological contact allergies and act favorably to suppress transplantation immunological responses. The immunosuppressive agents that are presently employed, however, generally reveal a strong cytotoxicity and exhibit marked side effects. Thus, these drugs would not be preferable in the therapy of chronic allergic diseases or autoimmune diseases in which long-term administration may be required.
The present inventors discovered that some salicylanilide derivatives possess strong inhibitory activities toward the enzyme histidine decarboxylase which catalyzes the conversion of histidine to histamine and are useful as a therapeutic agent in allergic diseases and inflammation which may be mediated by histamine and that is disclosed in U.S. Pat. application Ser. No. 461,772 filed on Apr. 17, 1974.
It has been known that an inhibitor of histidine decarboxylase such as 2-hydrazino-3-(4-imidazolyl)-propionic acid [Chem. Abst. 76, 135672k, (1972)] or tritoqualine [Arerugi 22, 640-8 (1973) Japan] inhibits antibody formation, anaphylaxis or contact dermatitis, but these antiallergic actions may not be associated with its inhibition of histidine decarboxylase.
The present inventors further continued pharmacological search with a series of benzanilide derivatives including the above-presented salicylanilide derivatives and others, and found that the compounds specified in this invention exhibit the suppressive effects of humoral and/or cell-mediated immunity. These compounds are not cytotoxic and have low toxicity allowing long-term administration for the therapy of such diseases as autoimmune diseases.